This presentation is about the functioning of G-Protein coupled receptors. It also gives necessary information about the G-protein and it functions. It ends by explaining some of the faults associated with GPCR (G-PROTEIN COUPLED RECEPTORS).
This presentation is about the functioning of G-Protein coupled receptors. It also gives necessary information about the G-protein and it functions. It ends by explaining some of the faults associated with GPCR (G-PROTEIN COUPLED RECEPTORS).
General principles of signal transduction
G Protein-coupled Receptors (GPCRs): Structure and Mechanism.
GPCRs that Regulate Adenylyl Cyclase.
GPCRs that Activate Phospholipase C.
GPCRs that Regulate Ion Channels.
GPCRs that Regulate Gene Transcription.
1.WHAT ARE GPCRs
2. CLASSIFICATION OF GPCRs
3. GPCRs SECOND MESSENGERS
4. GPCRs FAMILIES
5. STRUCTURE IF GPCRs
6. DRUG TARGETS OF GPCRs
7. CONCLUSION
8. REFERENCES
9. THANKS
Carbohydrates are the sugars, starches and fibers found in fruits, grains, vegetables and milk products. Though often maligned in trendy diets, carbohydrates — one of the basic food groups — are important to a healthy diet.
For More Medicine Free PPT - http://playnever.blogspot.com/
For Health benefits and medicine videos Subscribe youtube channel - https://www.youtube.com/playlist?list=PLKg-H-sMh9G01zEg4YpndngXODW2bq92w
In this informative webinar, with expert nutritionist Dr Nina Bailey, you will learn about how we can optimise our diet to help manage depressive symptoms:
- Foods the brain needs to function: what we should be eating
- Foods that starve the brain of nutrients: what foods we really need to avoid
- Food, mood and money: how to eat well on a budget
- Supplements: the best nutrients for depression, backed up by science
By making some relatively simple dietary changes that may, in some cases, include the use of dietary supplements, it is possible to see significant improvement in symptoms.
General principles of signal transduction
G Protein-coupled Receptors (GPCRs): Structure and Mechanism.
GPCRs that Regulate Adenylyl Cyclase.
GPCRs that Activate Phospholipase C.
GPCRs that Regulate Ion Channels.
GPCRs that Regulate Gene Transcription.
1.WHAT ARE GPCRs
2. CLASSIFICATION OF GPCRs
3. GPCRs SECOND MESSENGERS
4. GPCRs FAMILIES
5. STRUCTURE IF GPCRs
6. DRUG TARGETS OF GPCRs
7. CONCLUSION
8. REFERENCES
9. THANKS
Carbohydrates are the sugars, starches and fibers found in fruits, grains, vegetables and milk products. Though often maligned in trendy diets, carbohydrates — one of the basic food groups — are important to a healthy diet.
For More Medicine Free PPT - http://playnever.blogspot.com/
For Health benefits and medicine videos Subscribe youtube channel - https://www.youtube.com/playlist?list=PLKg-H-sMh9G01zEg4YpndngXODW2bq92w
In this informative webinar, with expert nutritionist Dr Nina Bailey, you will learn about how we can optimise our diet to help manage depressive symptoms:
- Foods the brain needs to function: what we should be eating
- Foods that starve the brain of nutrients: what foods we really need to avoid
- Food, mood and money: how to eat well on a budget
- Supplements: the best nutrients for depression, backed up by science
By making some relatively simple dietary changes that may, in some cases, include the use of dietary supplements, it is possible to see significant improvement in symptoms.
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
G PROTEIN COUPLED RECEPTORS(GPCRs) Cell Membrane ReceptorMerlin890676
G-protein coupled receptors (GPCRs)
Are cell membrane receptors
7 α-helical membrane spanning hydrophobic amino acid (AA) domain with 3 extracellular and 3 intracellular loops
The G-proteins has three subunits
α, β and γ
In the inactive state GDP is bound to the α subunit
Ligand binding activate the receptor and leads to displacement of GDP by GTP.
Three major effector pathways
(a) Adenylyl cyclase: cAMP pathway
(b) Phospholipase C: IP3-DAG pathway
(c) Channel regulation
Activation of AC by α subunit of Gs results in intracellular accumulation of second messenger cAMP
which functions through cAMP-dependent protein kinase (PKA).
The PKA phosphorylates and alters the function of many enzymes, ion
channels, transporters, transcription factors and structural proteins
to manifest as increased contractility/impulse generation (heart), relaxation (smooth muscle), glycogenolysis, lipolysis inhibition of secretion/mediator release, modulation of junctional transmission, water conservation by kidney, steroid hormone synthesis, etc.
Eg. Adrenaline
Inhibition of AC by α subunit of Gi results in inhibition of formation of second messenger cAMP
Opening of K+ channels
Eg. Acetyl choline M2 receptors
Activation of phospholipase Cβ (PLcβ) by α subunit of Gq hydrolyses
phospholipid phosphatidyl inositol 4,5-bisphosphate (PIP2)
to generate the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG).
The IP3being water soluble diffuses to the cytosol and mobilizes Ca2+ from endoplasmic reticular depots.
The lipophilic DAG remains within the membrane, but recruits protein kinase C (PKc) and activates it with the help of Ca2+.
The activated PKc phosphorylates many intracellular proteins and mediates various physiological responses.
Eg.Histamine H1 Receptor
The activated Gproteins (Gs, Gi, Go)
open or inhibit ionic channels specific for Ca2+ and K+ without the intervention of any second messenger like cAMP or IP3
bring about hyperpolarization/depolarization/changes in intracellular Ca2+ concentration.
The Gs opens Ca2+ channels in myocardium and skeletal muscles
while Gi and Go open K+ channels in heart and smooth muscle as well as inhibit neuronal Ca2+ channels
G-protein (Guanine nucleotide-binding proteins)
Regulatory proteins
Comprise of three subunits (γ), subunits possess GTPase activity.
G proteins belong to the larger group of enzymes called GTPases.
Regaulate guanine nucleotides GDP, GTP.
They bind and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP).
They are active 'on' when they are bound to GTP
They are inactive ‘off' when they are bound to GDP
receptor as drug target (receptor structure and signal transduction)Ravish Yadav
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Surgical Management of Obesity درمان جراحی چاقی
انواع اعمال جراحی :
محدود کننده جذب :
گاسترینگ باندینگ قابل تنظیم لاپاراسکوپیک
گاسترکتومی آسینی
مختل کننده جذب مواد غذایی :
انحراف صفراوی پانکراسی
سوئیچ دئودنال
ترکیبی :
بای پس معده
گاستریک باندینگ قابل تنظیم لاپاراسکوپیکLAGB
قرار دادن یک نوار سیلیکونی بادشونده دور قسمت پروگزیمال معده که نوار به یک سیستم مخزنی که اجازه تنظیم سفتی نوار را فراهم می آورد متصل می شود. این سیستم مخزنی به وسیله یک پورت زیرجلدی قابل دسترس می شود.
دونوع نوار برای این روش استفاده می شود :
lap-bandگاستریک باندینگ قابل تنظیم
گاستریک باندینگ قابل تنظیم سوئدی
این عمل جراحی بیشتر به صورت سرپایی انجام می شود وچون دستگاه گوارش مورد تهاجم قرار نمی گیرد خطر نسبی این عمل کمتر از اعمال دیگر است.
بیمارانی که برای کاهش وزن ناشکیبا هستند ، بی تحرک هستند ، قادر به ورزش نیستند و انتظار دارند که بتوانند به عادات غذایی قبلی خود بدون تغییر ادامه دهند کاندید خوبی برای این عمل نیستند.
تنظیمات باند و جلسات گروه حمایتی پس از عمل برای نتایج خوب بسیار مهم هستند.تنظیمات باند مانند بخشی از جراحی مهم است.
توافق کلی این است که کاهش کمتر از دو پوند در هفته اندیکاسیون افزایش محدودیت باند با اضافه کردن مایع است.
نتایج:
به طور میانگین 5تا7 سال بعد از عمل بیماران به ترتیب 60% و 58% از وزن اضافی را کم کردند.
هایپرتانسیون در 55% بیماران طی یک سال برطرف شده
آپنه انسدادی به 2%کاهش داشته
آسم و افسردگی بهبود داشته
در بیش از 50% موارد بهبودی داشته GERD
عوارض:
- پرولاپس: قسمت تحتانی معده به سمت بالا هل داده شده و در لومن باند گیر می کند.نیازبه جراحی دوباره دارد.
- سرخورردن
- صدمه بافتی به خاطر فرسودگی باند
- عوارض پورت و لوله هاَ
شکست در کاهش وزن بیشتر از اعمال دیگر رخ می دهد.
در عکسی بالا سمت چپ می تونید تصویر سلول های مخروطی و استوانه ای رو مشاهده کنید. مقدار پراکندگی سلول های مخروطی و استوانه ای رو مشاهده می کنید که به چه ترتیبی است. در لکه زرد تراکم سلول های مخروطی فوق العده زیاده که البته در لکه زرد بیشتر دو نوع مخطروط سبز و قرمز رو می بینیم تا آبی. گسترش آبی در مناطق غیر از لکه زرد هم وجود داره به همین دلیل هست که نقشه پری متری گستره دید رنگ آبی رو بیش از بقیه رنگ ها نشون میده.
مخروط های آبی و قرمز و سبز واقعا این به این رنگ ها حساس نیستند. در نموداری که مشاهده می کنید، مقدار جذب نوری هر سلول در فرکانس های مختلف نشون داده شده. بیشترین جذب نوری آب در بنفش، سبز در سبز و قرمز در زرد است. لذا پیگمان های اینها رو وقتی نام گذاری می کنند گاها به پیگمان قرمز، پیگمان زرد گفته می شود. دقت کنید که فارق از نوع سلول ها اگه بخواهیم شدت جذب نوری برای مجموعه سلول ها رو رسم کنیم قله نمودار روی خول و حوش رنگ سبز قرار می گیره و بیشترین جذب نوری چشم روی رنگ سبز قرار می گیرد.
Small,medium,large wavelength absorbance
Rods most absorbance but iin low intensity
Forming of color: n % of red+n% green = orange
پیگمان ها رو با نام های ال و اس و ام هم نشون میدن. سلول های مخروطی با اینکه برای رنگ خاصی حساسیت ندارند ولی مشاهده می کنید که در یک گستره فرکانس جذب بیشتری دارند ولی خوب ویژگی این سلول ها اینه که در شدت های پایین نوری جذب از مجموعه نوری دارند و لذا نور را تشخیص می دهند تا رنگ.
برای ایجاد رنگ های مختلف در ذهن ما باید ترکیبی از سلول ها تحریک شوند مثلا برای نارنجی باید مقدار سلول قرمز و سبز تحریک شود و آبی تحریک نشود.
رنگ های اصلی و مکمل در نورپیش از پرداختن به این مفاهیم باید به این نکته توجه کنیم که در این بحث با رنگ نور سر و کار داریم و نه با رنگ های شیمیایی که مثلا در نقاشی مورد استفاده قرار می گیرند. قوانین حاکم بر ترکیب رنگ های شیمیایی (ترکیب کاهشی) با ترکیب نورهای رنگی (ترکیب افزایشی) متفاوت است.
بر
,vasectomy ,nsv ,وازکتومی ,بیضه ,scrutom ,vas deferens ,epididymis ,اپیدیدیم
قطع وازودفران كه با عمل جراحی ساده بدون بیهوشی عمومی در مدتی كوتاه (15-20 دقیقه) انجام میشود.
امروزه وازکتومی، بدون استفاده از تیغ جراحی صورت میگیرد و نیازی به بخیهزدن ندارد.
بسته شدن لوله های اسپرم بر
مكانيسم:
جلوگیری از ورود اسپرم به مایع منی
وازکتومی بدون تیغ جراحی(ان اس وی):
-بی حسی موضعی روی خط میانی کیسه بیضه ها در یک نقطه و گشاد کردن سوراخ تزریق به اندازه ته سنجاق قفلی کوچک(حدود چهار میلی متر)
-بیرون آوردن هر دو لوله وازودفران راست و چپ توسط دو پنس مخصوص از این
سوراخ(حدود یک سانتی متر)
-قطع وازودفران و بستن سر لوله ها با نخ
-عدم نیاز به بخیه سوراخ ایجاد شده به دلیل کوچک بودن
No-needle anesthesia: Fear of needles for injection of local anesthesia is well known.[7] In 2005, a method of local anesthesia was introduced for vasectomy which allows the surgeon to apply it painlessly with a special jet-injection tool, as opposed to traditional needle application. The numbing agent is forced/pushed onto and deep enough into the scrotal tissue to allow for a virtually pain-free surgery. Initial surveys[7] show a very high satisfaction rate amongst vasectomy patients. Once the effects of no-needle anesthesia take effect, all other aspects of the vasectomy surgery remain the same.
A jet injector is a type of medical injecting syringe that uses a high-pressure narrow jet of the injection liquid instead of a hypodermic needle to penetrate theepidermis. It is powered by compressed air or gas, either by a pressure hose from a large cylinder, or from a built-in gas cartridge or small cylinder.
Jet injectors are used for mass vaccination, and as an alternative to needle syringes for diabetics to inject insulin. As well as health uses, similar devices are used in other industries to inject grease or other fluid.
بر اساس who راحت ترین و بهترین روش پیشگیری از بارداری وازکتومی است.راحت است : کوتاه و بدون تیغ جراحی و بخیه. بهترین : چون بازدهی بالایی دارد.
در مقابل وازکتومی لفظ castration یا خته کردن هست که در گذشته انجام میشده و البته برای حیوانات هنوز استفاده میشه. و دو نوع فیزیکی و شیمیایی دارد.
post-vasectomy pain syndrome : Sperm Granulomatosis in entry of sperm to scrutom and making antisperm Ig in body.
در مدل هایی که دو سر بسته می شو�
Open-ended vasectomy: The testicular end of the vas deferens is not sealed, which allows continued streaming of sperm into the scrotum. This method may avoid testicular pain as a result of increased back-pressure in the epididymis.
Vas occlusion techniques
Intra-Vas device: The vasa deferentia can also be occluded by an Intra-Vas device or "IVD".
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
5. • Large G-Proteins (Heterotrimeric G Proteins)
• In G protein-coupled receptors (GPCR)
• 3 Subunits : α, β, γ
• Small G-Proteins (Momomeric G Protein)
• Subunit : α
6. GPCR or GPLR
(G protein coupled receptors) (G protein linked receptors)
• seven-transmembrane domain receptors
(7TM receptors)
• heptahelical receptors
• serpentine receptor
7. Binding ligand
Changing conformation of GPCR
Acting GPCR as GEF (guanine nucleotide exchange
factor )
8. Exchanging GDP for a GTP (inside the cell) &
Activating G protein
Dissociating the subunit α binding GTP from β & γ
subunits
9. Affecting subunit α to intracellular signaling
proteins(Effect Protein) or target functional
proteins directly (finally a cascade) depending on
the α subunit type
10. Pathways :
Changing Polarization of membrane by Activating
or Inactivating chanells.
cAMP
IP3 & DAG
11.
12.
13. Types of α subunit :
• Gi/o
• Gz
(αi, αo)
(αz)
Inhibition of Adenylate Cyclase
Change K+-channels gating
Change Ca2+-channels gating
Inhibition of Adenylate Cyclase
& Activation of
phosphodiesterase (PDE)
14. Types of α subunit :
• Gi/o (αi, αo)
Inhibition of Adenylate Cyclase
Change K+-channels gating
Change Ca2+-channels gating
21. protein kinase A (PKA)
Phosphorilation
ADH : Promotes water
retention by the kidneys
GHRH & GHRIH : Stimulates & inhibits the
synthesis and release of GH
CRH : Stimulates the synthesis and release of ACTH
ACTH : Stimulates the synthesis
and release of Cortisol
TSH : Stimulates the synthesis and
release of a majorityof T4
Glucagon : Stimulates
glycogen breakdown
LH & FSH : Stimulates follicular
maturation and ovulation
Calcitonin : Decreases
blood calcium levels
PTH & Calcitonin :
Increasing & Decreases
blood calcium levels
Glucagon : Stimulates lipogenesis
Glucagon : Stimulates
Insulin synthesis
22. Types of α subunit :
• Go
• Gt
• Ggust
(αolfactory)
(αtransdusin)
(αgastdusin)
Activation of AC
23.
24.
25. Types of α subunit :
• Gq
• G12/13
(αq , α11 , α14 ,
α15 , α16 )
(α12, α13)
Activation of PhosphoLipase C
(PLC)
Activation of Rho family of
GTPases
26. Some example of these receptors :
• NEP ( α1 receptor)
• TRH receptors
• GnRH receptors
• Vasopressin (ADH in all organ except kidney receptors)
• Histamin (H1 receptor)
• Acetylcholine M1, M3, M5 muscarinic receptors
• Angiotensin II receptor (type 1)
• Calcitonin receptor
27. Gq ► Effector protein : Phospholipase C (PLC)
Cleavege membrane Phosphoinositol (PIP2)
DAG IP3
Activation of
protein kinase C
Release of
intracellular Ca2+
Regulation of other enzymes
(by protein phosphorylation)
Regulation of other enzymes
(by Ca2+)
Vasopressin (ADH) :
Induces vasoconstriction
TSH : Induces the synthesis and
release of a small amount of T4
Angiotensin II : Induces
Aldosterone synthesis and release
TRH : Induces the synthesis
and release of TSH
GnRH : Induces the synthesis
and release of FSH and LH
28.
29. G12/13 ► Effector protein : Rho Protein
(specially in Fibroblasts)
Activating Rho protein
Various action e.g. :
• Polimerization microtubule & microfilament (Actin)
• Remoding Sytoskeleton & Changing cell shape (&
regulating cell migration, phagocytosis,…)
• Function in cell cycle (mitosis & cytokinesis)
• Controling cell polarity
• Vesicular trafficking
• Apoptosis
• Wound healing
▼
30. G βγ (Beta-gamma complex)
• Inhibition of the Gα subunit
• Activate G protein coupled Inward-Rectifying
Potassium Channels (Kir, GIRK)
• Activation of PLA2 when bound to histamine receptors
• Activating PLC, as a minor mechanism of GHRH
• Activation L-type calcium channels
32. -Inherent GTPase activity of G-protein
Slow GTP hydrolasis capability of
Gα
associating Gβγ
Allostrically Exchanging GTP/GDP
-Regulator of G protein signalling (RGS)
or GTPase-activating proteins (GAP)
-GAP activity of Effector (PLC or AC)
33. Small G Protein
• Small protein (20-kDa to 25-kDa)
• binding to guanosine triphosphate (GTP) = activation
• homologous to Ras GTPases
(also called the Ras superfamily GTPases)
GTP-Binding Protein is wrong becouse some time it is GDP -Binding
Speak about GPLR in futur
With Techer last session Explanation & what you know
Alpha . Functional subunit & binding to GTP
G proteins belong to the larger group of enzymes called GTPases
α), beta (β), and gamma (γ) . There are also "small" G proteins (20-25kDa) that belong to the Ras superfamily of small GTPases. These proteins are homologous to the alpha (α) subunit found in heterotrimers, and are in fact monomeric. However, they also bind GTP and GDP and are involved in signal transduction.
Binding ligand to a domain located outside the cell
the GEF domain, in turn, allosterically activates the G-protein by facilitating the exchange of a molecule of GDP for GTP at the G-protein's α-subunit
-----------------
The G protein-coupled receptor kinases (GRKs) are protein kinases that phosphorylate only active GPCRs.
Phosphorylation of the receptor can have two consequences:
1.Translocation: The receptor is, along with the part of the membrane it is embedded in, brought to the inside of the cell, where it is dephosphorylated within the acidic vesicular environment[39] and then brought back. This mechanism is used to regulate long-term exposure, for example, to a hormone, by allowing resensitisation to follow desensitisation. Alternatively, the receptor may undergo lysozomal degradation, or remain internalised, where it is thought to participate in the initiation of signalling events, the nature of which depend on the internalised vesicle's subcellular localisation.[38]
2.Arrestin linking: The phosphorylated receptor can be linked to arrestin molecules that prevent it from binding (and activating) G proteins, effectively switching it off for a short period of time. This mechanism is used, for example, withrhodopsin in retina cells to compensate for exposure to bright light. In many cases, arrestin binding to the receptor is a prerequisite for translocation. For example, beta-arrestin bound to β2-adrenoreceptors acts as an adaptor for binding with clathrin, and with the beta-subunit of AP2 (clathrin adaptor molecules); thus the arrestin here acts as a scaffold assembling the components needed for clathrin-mediated endocytosis of β2-adrenoreceptor
Binding ligand to a domain located outside the cell
the GEF domain, in turn, allosterically activates the G-protein by facilitating the exchange of a molecule of GDP for GTP at the G-protein's α-subunit
-----------------
The G protein-coupled receptor kinases (GRKs) are protein kinases that phosphorylate only active GPCRs.
Phosphorylation of the receptor can have two consequences:
1.Translocation: The receptor is, along with the part of the membrane it is embedded in, brought to the inside of the cell, where it is dephosphorylated within the acidic vesicular environment[39] and then brought back. This mechanism is used to regulate long-term exposure, for example, to a hormone, by allowing resensitisation to follow desensitisation. Alternatively, the receptor may undergo lysozomal degradation, or remain internalised, where it is thought to participate in the initiation of signalling events, the nature of which depend on the internalised vesicle's subcellular localisation.[38]
2.Arrestin linking: The phosphorylated receptor can be linked to arrestin molecules that prevent it from binding (and activating) G proteins, effectively switching it off for a short period of time. This mechanism is used, for example, withrhodopsin in retina cells to compensate for exposure to bright light. In many cases, arrestin binding to the receptor is a prerequisite for translocation. For example, beta-arrestin bound to β2-adrenoreceptors acts as an adaptor for binding with clathrin, and with the beta-subunit of AP2 (clathrin adaptor molecules); thus the arrestin here acts as a scaffold assembling the components needed for clathrin-mediated endocytosis of β2-adrenoreceptor
Ophen this 2 path ways
Ophen this 2 path ways
Dicrease c AMP----opening k+ channels by beta,gamma subunit
Inhibitory.other.zeta
Dicrease c AMP----opening k+ channels by beta,gamma subunit
Inhibitory.other.zeta
Opening K+-channels
Closing Ca2+-channels
Dicrease c AMP----opening k+ channels by beta,gamma subunit
Inhibitory.other.zeta
Increase cAMP
Increase cAMP
EP & NEP
Effector Pro : Adenilat Cyclase
PKA is also known as cAMP-dependent protein kinase
Gi:Dicrease cAMP :NEP (alpha2 receptor),somatostatin(GHRIH),PIH, Histamin (H3,H4 Receptor), Acetylcholine M2 & M4 receptors, Dopamine D2, D3, D4,GABAB receptor, Prostaglandin EP1, EP3, FP, & TP receptors
Gs:Increase CAMP : glucagon.ADH.LH.FSH. Histamin (H2 Receptor),NEP (B1-Adrenergic receptor),CRH,GHRH
Dicrease c AMP----opening k+ channels by beta,gamma subunit
Inhibitory.other.zeta
Rhodopsin
Taste receptors
Rho is Ras homologus gene
The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic organisms including yeasts and some plants. Three members of the family have been studied a great deal: Cdc42, Rac1, and RhoA. Rho proteins have been described as "molecular switches" and play a role in cell proliferation,apoptosis, gene expression, and multiple other common cellular functions
IP3: TRH,GnRH.Vasopressin,NEP(alpha 1 receptor),Histamin(H1 receptor)
IP3 acts on IP3 receptors found in the membrane of the endoplasmic reticulum (ER) to elicit Ca2+release from the ER, while DAG diffuses along the plasma membrane where it may activate any membrane localized forms of a second ser/thr kinase called Protein Kinase C (PKC)
Regulators
Apoptose-changing conformation cause to flip flop plc(cholin) to pls(serin)
Three general classes of regulators of rho protein signaling have been identified: guanine nucleotide exchange factor (GEFs), GTPase-activating proteins (GAPs) and guanine nucleotide dissociation inhibitors (GDIs)[8]. GEFs control the release of GDP from the rho protein and the replacement with GTP. GAPs control the ability of the GTPase to hydrolyze GTP to GDP, controlling the natural rate of movement from the active conformation to the inactive conformation. GDI proteins form a large complex with the rho protein helping to prevent diffusion within the membrane and into the cytosol, thus acting as an anchor and allowing for very specific spatial control of rho activation[8].
---
Ligand that cause this changes like FGF,WNT,… (Embriogenesis)
-----
Cellular shape for example : Mental retardation is because of malfunction of dendritic spine may be result of disorder in rho protein
------------
Cancer : malfunction of rho protein. Increaseing mitosis,
Regulators
Apoptose-changing conformation cause to flip flop plc(cholin) to pls(serin)
Three general classes of regulators of rho protein signaling have been identified: guanine nucleotide exchange factor (GEFs), GTPase-activating proteins (GAPs) and guanine nucleotide dissociation inhibitors (GDIs)[8]. GEFs control the release of GDP from the rho protein and the replacement with GTP. GAPs control the ability of the GTPase to hydrolyze GTP to GDP, controlling the natural rate of movement from the active conformation to the inactive conformation. GDI proteins form a large complex with the rho protein helping to prevent diffusion within the membrane and into the cytosol, thus acting as an anchor and allowing for very specific spatial control of rho activation[8].
---
Ligand that cause this changes like FGF,WNT,… (Embriogenesis)
-----
Cellular shape for example : Mental retardation is because of malfunction of dendritic spine may be result of disorder in rho protein
------------
Cancer : malfunction of rho protein. Increaseing mitosis,
The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, andneurotransmitters, and vary in size from small molecules topeptides to large proteins
light and olfactory stimulatory molecules);adenosine, bombesin, bradykinin, endothelin, γ-aminobutyric acid (GABA), hepatocyte growth factor (HGF), melanocortins, neuropeptide Y, opioid peptides,opsins, somatostatin, GH, tachykinins, members of thevasoactive intestinal peptide family, and vasopressin;biogenic amines (e.g., dopamine, epinephrine,norepinephrine, histamine, glutamate (metabotropiceffect), glucagon, acetylcholine (muscarinic effect), andserotonin); chemokines; lipid mediators of inflammation(e.g., prostaglandins, prostanoids, platelet-activating factor, and leukotrienes); and peptide hormones (e.g.,calcitonin, C5a anaphylatoxin, follicle-stimulating hormone (FSH), gonadotropin-releasing hormone (GnRH), neurokinin, thyrotropin-releasing hormone (TRH), and oxytocin
GPCRs that act as receptors for stimuli that have not yet been identified are known as orphan receptors.
Exchanging GTP/GDP & reassociat alpha subunit to gamma beta subunit
GAP activity of Effector in Gq family (PLC)
Lipidation
In order to associate with the inner leaflet of the plasma membrane, many G proteins and small GTPases are lipidated, that is, covalently modified with lipid extensions. They may be myristolated, palmitoylated or prenylated.
میدانیم پروتینهای غشایی در سه دسته تقسیم بندی میشوند. دسته اول پروتئینهای اینتگرال .دسته دوم پروتئین های پریفرال.و نهایتا دسته سوم پروتئینهای لنگر انداخته به لیپید که خود به سه گروه تقسیم می شوند :
۱. اتصال یافته به سطح سیتوزولی غشای پلاسما توسط میریستات (myristate )
۲. اتصال یافته به سطح سیتوزولی غشای پلاسما توسط فارنیسیل (farnesyl )
۳. اتصال یافته به سطح خارج سلولی غشای پلاسما توسط گلیکوزیل فسفاتیدیل اینوزیتول
شکل 2-F-6 . نمایشی از anchor ها که توسط برخی پروتئین ها به غشای پلاسمایی متصل شده اند. v-Src نوعی از پروتئین تیروزین کیناز غیر وابسته به رسپتور می باشد که شامل سیگنال دهی سلول می شود. پروتئین Ras نقش مهمی را در سیگنال دهی سلولی ایفا می کند.
Small GTPases are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a form of G-proteins found in the cytosol which are homologous to the alpha subunit of heterotrimeric G-proteins, but unlike the alpha subunit of G proteins, a small GTPase can function independently as a hydrolase enzyme to bind to and hydrolyze a guanosine triphosphate (GTP) to form guanosine diphosphate (GDP). The most well-known members are the Ras GTPases and hence they are sometimes called Ras superfamily GTPases.
G proteins regulate metabolic enzymes, ion channels, transporters, and other parts of the cell machinery, controlling transcription, motility, contractility, and secretion, which in turn regulate systemic functions such as embryonic development, learning and memory, and homeostasis
G proteins are important signal transducing molecules in cells. "Malfunction of GPCR [G Protein-Coupled Receptor] signaling pathways are involved in many diseases, such as diabetes, blindness, allergies, depression, cardiovascular defects, and certain forms of cancer. It is estimated that more than half of the modern drugs' cellular targets are GPCRs